Pyrazine ring closure, oxidative

Pyrazines are obtained by oxidative ring closure of bis(acylmethyl)amines (304) with ammonia. 

Bourguignon and coworkers in their preparation of thieno[2,3-6]pyrazine used methyl-pyrazine (364 Scheme 107) (80JHC257) as starting material. The chlorination of (364) yields 2-chloro-3-methyl- and 2-chloro-6-methyl-pyrazine in a ratio of 80 20. Without separation this mixture is treated with ethyl mercaptoacetate in the presence of sodium ethoxide to give (365) in 91% yield (based on 2-chloro-3-methylpyrazine). Oxidation of the methyl group to an aldehyde function and subsequent base catalyzed ring closure yields (366), which is transformed to (363) by the method depicted already in Scheme 106. 

Preparations of pyrazine A -oxides containing extranuclear hydroxyl groups are also described in Qiapter III as follows Section III.l, 2-aminopyrazine 1-oxides from a-amino nitriles and a-hydroxyimino carbonyl compounds (540, 541) Section III.2, 3-substituted pyrazine 1-oxides from 2-amino-2-deoxy-D-glucose(or mannose) oxime with glyoxal (543, 544) and Section III.5, ring closure of the C-C-N-C-C-N-0 system (553). 

The oxidations of 2-amino-3-cyanopyrazine 1-oxides to the 1,4-dioxides are described in Section VIII.3A(4) and deoxygenations of some 2-amino-3-cyano-pyrazine 1-oxides and 1,4-dioxides with phosphorus trichloride or sodium dithionite in Section VIII.3C(4). Deoxygenation and chlorination of aminocyanopyrazine 1-oxides are reported in Section V.IG, and deoxygenation and acetoxylation or alkoxylation of 2-amino-3-cyano-5-methylpyrazine 1,4-dioxide in Section VIII.3C(5). Hydrolysis of cyanopyrazine Y-oxides to carbamoylpyrazine Af-oxides are given in Section 10A(3) and ring closure reactions of 2-amino-3-cyanopyrazine 1-oxides to pteridine 8-oxides in Section V11I.3C(3). 

Phenyl-[l,2,4]triazolo[l,5-(2]pyrazines have been prepared by the oxidative ring closure of iV(2)-pyrazinylbenzamldines (344) as shown in Scheme 60. The benzamidines were synthesized from 2-aminopyrazines and benzonitrile, a reaction that failed with aliphatic nitriles (64JOC2542). 

Oxidative photocyclization of l-(2-naphthyl)-2-(3-phenanthryl)ethylene has been carried out in a chiral liquid crystal and an optically active helicene obtained. A synthetically useful conversion of 2-()S-arylvinyl)pyrazines to azaphenanthrenes has also been described using the same oxidative procedure. The position at which ring closure occurs is dependent on the structme of the aryl group. 

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